Renin in the absence of a grossly elevated blood level has been shown to maintain elevated blood pressure in experimental hypertension where one kidney is clamped, the other intact (two-kidney model). Inhibitors of the renin-angiotensin system are now available: antirenin serum; pepstatin, an enzyme blocker; SQ 20858, which inhibits angiotensin I conversion to angiotensin II; and an unidentified material contained in renal medullary extracts. A systematic examination of the antihypertensive effects of these substances is planned for the two- kidney hypertension model and for the one-kidney model (one renal artery clamped, opposite kidney removed), a form of hypertension which is alleged to be not renin-dependent. If renin is causative of two-kidney hypertension, in the absence of a high blood level, this may be the result of a) an augmented renin turnover, or b) extravascular renin accumulation as in the kidney or brain. These hypotheses will be tested a) by standard techniques to measure turnover rates and b) by localized intraarterial injections of antirenin. Finally, the hypothesis will be examined that renal medullary extracts are effective by blocking the renin-angiotensin system. The role of prostaglandins in the antihypertensive effect of renal medullary extracts will be intensively investigated.